A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors

Breast Cancer Clinical Trial

Official title:

A PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07220060 IN COMBINATION WITH PF-07104091 PLUS ENDOCRINE THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05262400
• Other study ID #: C4391002
• Secondary ID: 2022-002173-28
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 14, 2022
• Est. completion date: December 29, 2026

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07220060 and PF-07104091) in people with breast cancer. This clinical study consists of 2 parts (part 1 and part 2). In part 1, we are seeking participants who:

• Have been diagnosed with Breast Cancer (BC) of either types:

• Have HR+, HER2- BC

• Refractory HR-positive/HER2-positive BC

• Have other solid tumors other than BC

In part 2, we are seeking participants who:

-Have HR-positive/HER2-negative BC Part 1 will include increasing doses of PF-07220060 with PF-07104091. In part 2, participants will take 1 of 2 study medicine combinations. This will help us decide the highest amount of study medicines that can be safety given to people. All participants in this study will receive PF-07220060 with PF-07104091 by mouth. We will compare participant experiences to help us determine if PF-07220060 with PF-07104091 is safe and effective. Participants will take part in this study for about 2 years. During this time, they will receive the study medicine, an x-ray imaging, and will be observed for safety and effects of the study medicines.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 29, 2026
• Est. primary completion date: December 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Part 1: Breast Cancer (BC)

• HR+, HER2- BC

• Refractory HR-positive/HER2-positive BC

• Part 1: Solid Tumors other than BC

• Part 2:

• HR-positive/HER2-negative BC

• Lesion:

• Part 1: evaluable lesion (including skin or bone lesion only)

• Part 2: measurable lesion per RECIST v1.1

• Prior systemic Treatment

• Part 1: HR-positive/HER2-negative BC

• At least 1 line of SOC, including CDK4/6 inhibitor therapy and Endocrine Therapy, for advanced or metastatic disease.

• Prior chemotherapy in the metastatic setting is allowed.

• Part 1: HR-positive/HER2-positive BC

• At least 1 prior treatment of approved HER2 targeting therapy.

• Part 1: Solid Tumors other than BC

• Participants with no standard therapy available or for which no local regulatory approved standard therapy is available that would confer significant clinical benefit in the medical judgement of the investigator.

• Part 2A: At least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and ET.

• Parts 2B: At least 1 prior endocrine therapy for advanced or metastatic disease. Progression during treatment or within 12 months of completion of adjuvant endocrine therapy is acceptable.

• Part 2B: Up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed.

• General Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1

• Adequate renal, liver, and bone marrow function

• Resolved acute effects of any prior therapy to baseline severity

Exclusion Criteria:

• All Study Parts: Permanent treatment discontinuation from prior CDK 4 and/or CDK2 inhibitor due to treatment related toxicity.

• Part 2B and 1C: Prior treatment with any CDK 4/6 inhibitor, or SERDs (e.g. fulvestrant), or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway for advanced disease.

• Parts 2B and 2C: Prior treatment with any CDK4/6 inhibitor for advanced disease.

• Parts 2B and 2C: Prior treatment with an investigational endocrine therapy for advanced disease.

• Part 2C: Prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.

• Part 2C: Any prior systemic treatment for advanced disease.

• Prior irradiation to >25% of the bone marrow

• Current use of drugs which have a risk for QTc prolongation

• Current use or anticipated need for food or drugs that are known strong CYP3A4/5, strong UGT2B7 or UGT1A9 inhibitors or inducers

• Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry

• Participants with any other active malignancy within 3 years prior to enrollment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen's disease

• Major surgery within 4 weeks prior to study entry

• Radiation therapy within 4 weeks prior to study entry.

• Clinically important hypertension

• Known or suspected hypersensitivity to PF-07220060, PF-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable)

• Known abnormalities in coagulation. Anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed

• Known active uncontrolled or symptomatic central nervous system (CNS) metastases

• Active inflammatory GI disease

• Current use or anticipated need for Proton Pump Inhibitors (PPI) within 14 days prior to first dose of the study intervention

• Previous high-dose chemotherapy requiring stem cell rescue

• Participants with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

• Other protocol specific exclusion criteria may apply

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Solid Tumors

Intervention

Drug:
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07104091 + PF-07220060 + fulvestrant dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
• PF-07104091 + PF-07220060 + fulvestrant dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with fulvestrant
• PF-07104091 + PF-07220060 + letrozole dose expansion
PF-07104091 and PF-07220060 will be administered orally in combination with letrozole
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally
• PF-07220060 + PF-07104091 combination dose escalation
PF-07104091 and PF-07220060 will be administered orally

Locations

Country	Name	City	State
Argentina	Centro Oncologico Korben	Buenos Aires
Argentina	Clínica Universitaria Reina Fabiola	Córdoba
Argentina	Fundación CORI para la Investigación y Prevención del Cáncer	La Rioja
Argentina	Clinica Viedma S. A	Viedma	RÍO Negro
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	SÃO Paulo
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia	Ijui	RIO Grande DO SUL
Brazil	Centro de Pesquisa Clínica - Área Administrativa	Porto Alegre	RIO Grande DO SUL
Brazil	Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa	Porto Alegre	RIO Grande DO SUL
Brazil	Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda	São Paulo
Bulgaria	Specialized Hospital for Active Treatment of Oncology - Haskovo	Haskovo
Bulgaria	Complex Oncology Center - Plovdiv EOOD	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment Serdika EOOD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment Serdika EOOD	Sofia	Sofia (stolitsa)
Bulgaria	Complex Oncology Center - Vratsa	Vratsa
China	The First Hospital of Jilin University	Changchun	Jilin
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
Czechia	Fakultni nemocnice Olomouc	Olomouc	Olomoucký KRAJ
Czechia	Fakultni nemocnice Bulovka	Prague	Praha 8
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Mexico	Mérida Investigación Clínica	Merida	Yucatán
Mexico	Instituto Nacional de Cancerologia	Mexico City	Distrito Federal
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEÓN
South Africa	FARMOVS	Bloemfontein	FREE State
South Africa	15 Eton Road	Johannesburg	Gauteng
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
South Africa	WCR Office	Johannesburg	Gauteng
South Africa	Wits Clinical Research	Johannesburg	Gauteng
South Africa	Wilgers Oncology Centre	Pretoria	Gauteng
Spain	Hospital Clínic de Barcelona	Barcelona	Catalunya [cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario HM Sanchinarro	Madrid	Madrid, Comunidad DE
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [LA Coruña]
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Administrative Address: UCLA Hematology/Oncology	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	UCLA Hematology/Oncology	Los Angeles	California
United States	UCLA Hematology / Oncology-Parkside	Santa Monica	California
United States	UCLA Hematology/Oncology-Santa Monica	Santa Monica	California
United States	Swedish Medical Center	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  China,  Czechia,  Mexico,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle	Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level	Cycle 1 (28 days)
Primary	Number of participants with treatment emergent adverse events (AEs)		From baseline until end of study treatment or study completion (approximately 2 years)
Primary	Incidence of participants with clinical laboratory abnormalities		From baseline until end of study treatment or study completion (approximately 2 years)
Primary	Number of participants with vital signs abnormalities		From baseline until end of study treatment or study completion (approximately 2 years)
Primary	Number of participants with corrected QT (QTc) interval	Determine the effect of the drug on QT prolongation. The number and percentage of participants who experienced QT interval prolongation will be summarized by dose level	From baseline until end of study treatment or study completion (approximately 2 years)
Secondary	Maximum plasma concentration (Cmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose		Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Time to maximum plasma concentration (Tmax) of PF-07220060 and PF-07104091 together after a single dose and multiple dose		Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07220060 and PF-07104091 together		Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Objective response rate (ORR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole	Percentage of participants with a best ORR of complete response (CR) or partial response (PR) using RECIST 1.	From baseline through disease progression or study completion (approximately 2 years)
Secondary	To evaluate the preliminary antitumor activity of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole by time to event endpoints	Time from first assessment of event endpoint to last assessment of using RECIST 1.1	From baseline through time to event on study or study completion (approximately 2 years)
Secondary	Duration of Response (DoR) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole	DoR is defined as the time from first documentation of CR or PR to date of first documentation of progressive disease/pharmacodynamic (PD) or death due to any cause, whichever occurs first	From baseline through time to event on study or study completion (approximately 2 years)
Secondary	Progression-Free Survival (PFS) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole	PFS is defined as time from start date of treatment to the date of first documentation of PD or death due to any cause	From baseline through time to event on study or study completion (approximately 2 years)
Secondary	Time to Progression (TTP) of PF-07220060 and PF-07104091 together in dose escalation and together in combination with fulvestrant or letrozole	TTP is defined as the time from start date of treatment to the date of the first documentation of PD	From baseline through time to event on study or study completion (approximately 2 years)

External Links

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